Understanding how industrialization reshapes the human metaorganism requires integrating microbiome ecology with host physiology across globally diverse populations. Here, we generate multivariate data from the Global Microbiome Conservancy cohort, including gut microbiome, immunoglobulin A (IgA) sequencing, host genotyping, diet, lifestyle, and fecal biomarker profiles, to investigate host-microbiome interactions across gradients of industrialization and geography. We show that industrialization is associated with homogenized microbial compositions, reduced microbial diversity, and lower community stability, independent of host confounders. We further show that industrialization is linked to elevated markers of gut stress, increased IgA secretion, and altered patterns of IgA-bacteria interactions. Finally, we show that microbiome-based disease predictors trained on industrialized populations are uninformative in less industrialized cohorts, highlighting limited cross-population transferability. Together, our results reveal coordinated restructuring of the microbial ecosystem and host physiology and emphasize the need for inclusive, globally representative data to improve translational microbiome applications across diverse human populations.